Toxicity of expanded polyglutamine-domain proteins in Escherichia coli

FEBS Letters
O OnoderaJ R Burke

Abstract

Five neurodegenerative diseases are caused by proteins with expanded polyglutamine domains. Toxicity of these proteins has been previously identified only in mammals, and no simple model systems are available. In this paper, we demonstrate in E. coli that long polyglutamine domains (59-81 residues) as GST-fusion proteins inhibit growth while smaller glutamine (10-35 residues) or polyalanine (61 residues) domains have no effect. Analogously in humans, polyglutamine repeats less than 35-40 glutamines produce a normal phenotype, while expansion greater than 40 glutamines is always associated with disease. Expression of polyglutamine proteins in E. coli may help identify the molecular mechanism of pathogenesis of CAG trinucleotide repeat diseases and be a useful screen to identify potential therapeutic compound.

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Citations

Dec 1, 1996·Current Opinion in Structural Biology·M F Perutz
Dec 16, 1997·Trends in Biochemical Sciences·R I Richards, G R Sutherland
Aug 6, 1999·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A LunkesJ L Mandel
Feb 15, 2000·Annals of the New York Academy of Sciences·Y NagaiJ R Burke
Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·J M LecerfJ S Huston
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y W ChenM F Perutz
Jan 24, 2006·Biochemical and Biophysical Research Communications·Kasturi L PuranamJames R Burke
Sep 10, 2014·Biochimica Et Biophysica Acta·Erwin De GenstChristopher M Dobson
Sep 23, 1997·Biochemical and Biophysical Research Communications·O OnoderaW J Strittmatter
Mar 23, 2010·Journal of Neuroscience Methods·Rhonda Husain-PonnampalamElsdon Storey
Oct 30, 2016·Protein Expression and Purification·Wen-Che TsaiHsiao-Wei Wen
Mar 21, 2002·FEBS Letters·Laura MasinoAnnalisa Pastore
Jul 14, 2017·Angewandte Chemie·Shusuke TomoshigeMinoru Ishikawa
Sep 6, 2018·Molecular Neurobiology·Catherine H Schein

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